IMMUNOPOTENTIATION OF A FOOT-AND-MOUTH DISEASE VIRUS SUBUNIT VACCINE BY INTERFERON ALPHA

Authors: BOTTON, SONIA - FED UNIV SANTA MARIA, BS; BRUM, MARIO - FED UNIV SANTA MARIA, BS; BAUTISTA-PECK, ELIDA - FORMER PIADC EMPLOYEE; Koster, Marla; WEIBLEN, RUDI - FED UNIV SANTA MARIA, BS; Golde, William; Grubman, Marvin

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/6/2006
Publication Date: 2/20/2006
Citation: Botton, S.D., Brum, M.C., Bautista-Peck, E.M., Koster, M.J., Weiblen, R., Golde, W.T., Grubman, M.J. 2006. Immunopotentiation of a foot-and-mouth disease virus subunit vaccine by interferon alpha. Vaccine. (2006) 24: 3446-3456.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of cloven-hoofed animals. Vaccines produced by chemical inactivation of virus are available, but there are concerns about their safety and about the ability to serologically distinguish vaccinated animals from infected animals. A possible alternative approach to develop safe, effective FMD vaccines is to produce viral subunit vaccines which do not contain infectious FMDV and lack the genetic information for a number of viral nonstructural proteins. We have used a replication-defective human adenovirus to deliver this vaccine (Ad5-FMDV). Thus, production of this vaccine does not require expensive high-containment manufacturing facilities, can be made in the U.S., which currently prohibits work with infectious FMDV on the mainland, and animals inoculated with this marker vaccine can readily be differentiated from infected animals using diagnostic assays employing the viral nonstructural proteins not present in the vaccine. In addition, we have previously shown that the antiviral agent type I interferon (IFN alpha) delivered by Ad5 can rapidly inhibit FMDV replication and within one day can protect swine from FMDV challenge. Therefore, the use of both an FMDV subunit vaccine and IFN alpha can result in rapid and long lasting protection and clear distinction between vaccinated and infected animals. It has also been shown by a number of groups that IFN alpha can act as an adjuvant and boost the immune response to various antigens. In this manuscript we examined the potential aduvant effect of IFN alpha when combined with an Ad5-FMD vaccine. Swine were inoculated with both the Ad5-FMD vaccine and Ad5-IFNalpha or with only the Ad5-FMD vaccine and challenged with FMDV 42 days later. The group inoculated with both the vaccine and IFN alpha had enhanced protection as compared to the group inoculated with only the vaccine. This information suggests that the addition of IFN alpha to a FMD control strategy can both induce rapid protection and boost the adaptive immune response.

Technical Abstract: The adjuvant effect of porcine interferon alpha (pIFN-a) was examined in swine vaccinated with a recombinant replication-defective adenovirus containing foot-and-mouth disease virus (FMDV) A24 capsid and 3C proteinase coding regions (Ad5-A24). Five groups of swine were inoculated with either high or low doses of Ad5-A24 in the presence or absence of Ad5-pIFNa or with a control Ad5 and challenged with FMDV at 42 days post vaccination. Animals receiving low-dose Ad5-A24 with no IFN had similar clinical disease, but only three of five animals developed viremia, while addition of IFN resulted in a delayed onset of lesions in three animals and only one animal had detectable viremia. Animals vaccinated with high-dose Ad5-A24 without IFN had no viremia, significantly fewer lesions and delayed onset of disease compared to the group given a low-dose vaccine and no IFN. Four of five pigs vaccinated with high-dose Ad5-A24 plus IFN were completely protected from disease and only one animal in this group had a lesion which was restricted to the site of challenge virus inoculation. Thus, pIFN-a enhances the long-term level of protection induced by the Ad5-FMD vaccine, supporting the use of IFN-a as a potential adjuvant in FMD vaccination strategies.